Prolonged and intensive medication use are associated with the obesity paradox after percutaneous coronary intervention: a systematic review and meta-analysis of 12 studies.
Obesity paradox is defined as the unexpected decrease in the total number of death which has been observed among patients who are overweight and obese compared to patients with normal weight after undergoing revascularization by percutaneous coronary intervention (PCI). Despite of so many recent studies which showed the existence of this phenomenon, prolonged and intensive medication use were only suggested to be among the reasons responsible for this 'obesity paradox' but it was never confirmed whether this hypothesis should really be considered true or not. Therefore, this study aimed to investigate whether prolonged and intensive medication use were associated with this obesity paradox after PCI. Medline, PubMed, EMBASE and the Cochrane Library were searched for studies showing the existence of this 'obesity paradox' in patients who underwent coronary revascularization by PCI and only articles comprising of medication use among the patients analyzed were considered relevant for this research. Medication use among the different subgroups of patients was calculated. Mortality was considered as the clinical endpoint in this study. Risk Ratio (RR) with 95 % Confidence Interval (CI) was used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. Twelve studies consisting of a total number of 91,582 patients was included in this meta-analysis. An intensive medication use after the hospital discharge and during the follow up period after PCI was observed in the subgroup of obese patients, followed by the overweight patients and the normal weight patients respectively. Our results showed that the short-term (30 days) mortality in overweight and obese patients was significantly lower compared to the normal weight patients with RR: 0.72; 95 % CI: 0.56-0.92, p = 0.008 and RR: 0.47, 95 % CI: 0.34-0.65; p < 0.00001 respectively. The long-term (≥ one year) mortality was also significantly lower in the overweight and the obese groups with RR: 0.74, 95 % CI: 0.67-0.82; p < 0.00001 and RR: 0.63, 95 % CI: 0.55-0.72; p < 0.00001 respectively. Our study has confirmed to some extent, that prolonged and intensive use of medications which were more prominent in patients who were overweight and obese during the follow up period, might apparently be among the reasons responsible for this obesity paradox after PCI.


Integrating a project monitoring system into a public health network: experiences from Alive & Thrive Vietnam.
Little information is available about how to build a monitoring system to measure the output of preventive nutrition interventions, such as counselling on infant and young child feeding. This paper describes the Alive & Thrive Vietnam (A&T) project experience in nesting a large-scale project monitoring system into the existing public health information system (e.g. using the system and resources), and in using monitoring data to strengthen service delivery in 15 provinces with A&T franchises. From January 2012 to April 2014, the 780 A&T franchises provided 1,700,000 counselling contacts (~3/4 by commune franchises). In commune franchises in April 2014, 80% of mothers who were pregnant or with children under two years old had been to the counselling service at least one time, and 87% of clients had been to the service earlier. Monitoring data are used to track the progress of the project, make decisions, provide background for a costing study and advocate for the integration of nutrition counselling indicators into the health information system nationwide. With careful attention to the needs of stakeholders at multiple levels, clear data quality assurance measures and strategic feedback mechanisms, it is feasible to monitor the scale-up of nutrition programmes through the existing routine health information system.


Sensing UV/blue: pterin as a UV-A absorbing chromophore of cryptochrome.
Cyanobacteria sense and respond to changes in an ambient light environment using highly specialized photoreceptors coupled to signal transduction pathways. Synechocystis sp. PCC 6803 is currently used as a model system to study light signal transduction in cyanobacteria. Recently, several important players, including photoreceptors and other signaling partners, have been identified in Synechocystis sp. PCC 6803. However, the nature of the molecules that act as UV/blue light sensors (and their downstream signaling mechanism) has not been elucidated. It has been postulated that pterins might serve as possible photoreceptor pigments for some behavioral responses induced by UV/blue light. By investigating the photomovement of wild-type and a pgtA mutant to UV/blue light, we demonstrated that cyanopterin is indeed involved in inhibiting negative phototaxis under UV/blue light. In this addendum, we provide additional evidence showing that the UV/blue action spectrum of the phototactic response coincides with the fluorescence spectrum of the in vivo cyanobacterial cryptochrome, DASH. Based on these results, we discuss the potential role of pterin as a UV-A absorbing chromophore of the cryptochrome in Synechocystis sp. PCC 6803.


Aortic deceleration injury treated by endograft: a case report with 11-year followup.
Aortic deceleration injury is a common and critical condition following automobile accident with high fatality. The survivors complicated with associated serious injuries are even rare and definitive treatment is required. A 37-year-old male patient had both aortic blunt injury and coronary artery injury after a frontal car collision. After failed coronary artery percutaneous transluminal angioplasty (PTA) and deteriorated aortic lesion, the ruptured aorta was subsequently successfully treated by us with a self-made individualized endograft. The endograft was well in position and the patient functioned well in 11-year followup. With the development of endograft and technique, the endovascular treatment may be an option for patients with complicated aortic blunt injury. Yet careful patient selection and the long-term followup are essential.


Convergent domestication of cereal crops by independent mutations at corresponding genetic Loci.
Independent domestication of sorghum, rice, and maize involved convergent selection for large seeds, reduced disarticulation of the mature inflorescence, and daylength-insensitive flowering. These similar phenotypes are largely determined by a small number of quantitative trait loci (QTLs) that correspond closely in the three taxa. The correspondence of these QTLs transcends 65 million years of reproductive isolation. This finding supports models of quantitative inheritance that invoke relatively few genes, obviates difficulties in map-based cloning of QTLs, and impels the comparative mapping of complex pheno-types across large evolutionary distances, such as those that separate humans from rodents and domesticated mammals.


Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition.
Healthcare systems worldwide are seriously challenged by a rising prevalence of neurodegenerative diseases (NDDs), which mostly, but not exclusively, affect the ever-growing population of the elderly. The most known neurodegenerative diseases are Alzheimer's (AD) and Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, but some viral infections of the brain and traumatic brain injury may also cause NDD. Typical for NDD are the malfunctioning of neurons and their irreversible loss, which often progress irreversibly to dementia and ultimately to death. Numerous factors are involved in the pathogenesis of NDD: genetic variability, epigenetic changes, extent of oxidative/nitrosative stress, mitochondrial dysfunction, and DNA damage. The complex interplay of all the above-mentioned factors may be a fingerprint of neurodegeneration, with different diseases being affected to different extents by particular factors. There is a voluminous body of evidence showing the benefits of regular exercise to brain health and cognitive functions. Moreover, the importance of a healthy diet, balanced in macro- and micro-nutrients, in preventing neurodegeneration and slowing down a progression to full-blown disease is evident. Individuals affected by NDD almost inevitably have low-grade inflammation and anomalies in lipid metabolism. Metabolic and lipid profiles in NDD can be improved by the Mediterranean diet. Many studies have associated the Mediterranean diet with a decreased risk of dementia and AD, but a cause-and-effect relationship has not been deduced. Studies with caloric restriction showed neuroprotective effects in animal models, but the results in humans are inconsistent. The pathologies of NDD are complex and there is a great inter-individual (epi)genetic variance within any population. Furthermore, the gut microbiome, being deeply involved in nutrient uptake and lipid metabolism, also represents a pillar of the gut microbiome-brain axis and is linked with the pathogenesis of NDD. Numerous studies on the role of different micronutrients (omega-3 fatty acids, bioactive polyphenols from fruit and medicinal plants) in the prevention, prediction, and treatment of NDD have been conducted, but we are still far away from a personalized diet plan for individual NDD patients. For this to be realized, large-scale cohorts that would include the precise monitoring of food intake, mapping of genetic variants, epigenetic data, microbiome studies, and metabolome, lipidome, and transcriptome data are needed.


Executive dysfunction in late-onset depression.
Depression in the elderly is frequently accompanied by cognitive impairment. Executive dysfunction, including disturbances in planning, sequencing, organizing and abstracting has been reported in late-onset depression. They were found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. A group of patients with late-onset depression, compared with age matched healthy volunteers, were assessed for deficits in executive functioning. We used the computer version of Stroop Color-Word test enabling more detailed reaction time analysis. Severity of depression was evaluated with Hamilton depression rating scale and Geriatric depression scale. The preliminary results of a study show that patients with late-onset depression have increased absolute reaction times in Stroop colour-word test. Significant differences in the magnitude of individual interference effects pointing towards a characteristic change in attentional processes in depressed patients. The preliminary results of a study comparing a group of elderly depressed patients with a control group of older healthy volunteers confirm changes in executive functions.


Biosafety and biosecurity challenges during the COVID-19 pandemic and beyond.
As the world continues to battle the SARS-CoV-2 pandemic, it is a stark reminder of the devastation biological threats can cause. In an unprecedented way the global community saw a massive surge in the demand for diagnostic capacities, which had a substantial impact on biosafety and biosecurity. Laboratories had to cope with a surge in laboratory testing capacity, while resources and training possibilities were limited. In addition, the pandemic highlighted the impact biological threats can have, thereby giving rise to new dialogue about biosecurity and new biological threats. This paper aims to highlight some of the most pressing issues regarding biosafety and biosecurity observed during the COVID-19 pandemic with special focus on low and lower middle-income countries. The authors provide lessons learned, tools and recommendations to improve future biosafety and biosecurity and increase preparedness for the next global health crisis.


Evaluating pharmacokinetics and pharmacodynamics of intravenous busulfan in pediatric patients receiving bone marrow transplantation.
BU is a commonly used conditioning agent in BMT. However, it is a narrow therapeutic index drug which shows a strong correlation between AUC and both efficacy and toxicity. Studies in pediatric patients have suggested that children less than four yr of age have a greater clearance and thus lower AUC at standard adult doses. The goal of this retrospective analysis was to evaluate any age-related pharmacokinetic and pharmacodynamic differences in pediatric patients who received BU as a conditioning agent. From 2003 to 2006, 21/77 pediatric patients who received BMT were reviewed. There were 15 males and six females with a mean age of six yr old. Diagnoses of leukemia (n = 11), Hodgkin's lymphoma (n = 3), myelodysplastic syndrome (n = 2), and other (n = 5) were included. Sixteen patients received BU + cyclophosphamide while five patients received BU + another agent. There were 20 allogeneic and one autologous transplants among which 16 were human leukocyte antigen matched and five were mismatched. Average BU clearance in patients younger than four yr old (n = 8) was 4.1 +/- 1.0 mL/min/kg vs. 3.1 +/- 0.7 mL/min/kg in patients older than four yr old (n = 13) (p = 0.02). The corresponding averages for AUC were 998 +/- 226 microm x min vs. 1155 +/- 183 microm x min (p = 0.12). No patients younger than four yr old developed VOD while five of the older patients did (p = 0.044). There were no significant differences in terms of engraftment and acute GvHD. There were significant age-related pharmacokinetic differences in pediatric patients less than four yr of age receiving BU for conditioning prior to BMT. There was a decrease in drug toxicity seen in these patients.


Pregnancy incidence, outcomes and associated factors in a cohort of women living with HIV/AIDS in Rio de Janeiro, Brazil, 1996-2016.
The aim of this research was to analyze pregnancy incidence and associated factors in a cohort of 753 women living with HIV/AIDS (WLWHA) in Rio de Janeiro, Brazil, from 1996 to 2016. Women aged 18-49 years who were not on menopause (surgical or natural) and did not have a tubal ligation were eligible for the study. Data were collected by medical professionals during initial and follow-up visits. Person-time pregnancy incidence rates were calculated throughout the follow-up period. Pregnancy incidence-associated factors were investigated by univariate and multiple analyzes, using an extension of the Cox survival model. Follow-up visits recorded 194 pregnancies, with an incidence rate of 4.01/100 person-years (95% CI: 3.47; 4.60). A higher pregnancy incidence was associated with CD4 nadir ≥ 350 cells/mm³, use of an antiretroviral regimen not containing Efavirenz, and prior teenage pregnancy. In turn, women with a viral load ≥ 50 copies/mL, age ≥ 35 years old, with two or more children and using a highly effective contraceptive method showed a lower incidence. Results showed a significant reduction in pregnancy incidence after 2006, a significant reduction in female sterilization from 1996 to 2016, and a high rate of cesarean sections. The association found between pregnancy incidence and the use of contraceptive methods and virological control markers suggests a good integration between HIV/AIDS and reproductive health services. The high rate of cesarean section delivery indicates the need to improve childbirth care.


Narcissism and the death instinct.
The myth of Narcissus is a myth of death resulting from the absence of desire in a love relationship, and a metaphor of the symbolic and imaginary death of the narcissistic person. Four of Freud's dreams are analysed in terms of their narcissistic structure. They reveal some important features in the implicit relationship between the feminine nature of the narcissistic body and the counterpart. They lead to a better formulation of the narcissistic state in terms of the relationship between the self and the counterpart. The narcissistic relationship is based on wishes and not desires. The object of the wish is not essential for the wish to emerge or to be sustained. As a result, the narcissistic relation is characterized by the absence of its aim and the impossibility of its satisfaction; and consequently it symbolizes death of the world or the self and is an imaginary death of both. In that sense, Freud's introduction of the concept of narcissism and his concept of the death instinct should be seen as connected, as they constitute a stage in psychoanalytic knowledge. It is difficult to understand narcissism detached from the concept of the death instinct without rendering the issues of meaning and interpretation irrelevant to the psychoanalytic act.


Lesions of the biceps pulley: diagnostic accuracy of MR arthrography of the shoulder and evaluation of previously described and new diagnostic signs.
To retrospectively determine the diagnostic accuracy of magnetic resonance (MR) arthrography of the shoulder in the evaluation of lesions of the biceps pulley and to evaluate previously described and new diagnostic signs. Institutional review board approval was obtained; the requirement for informed consent was waived. MR arthrograms of 80 consecutive patients (mean age, 34.2 years; 53 male, 27 female) with arthroscopically proved intact or torn pulley systems were assessed for the presence of a pulley lesion by three radiologists who were blinded to arthroscopic results. Criteria evaluated were displacement of the long head of the biceps tendon (LHBT) relative to the subscapularis tendon on oblique sagittal images (displacement sign), medial subluxation of the LHBT on transverse images, nonvisibility or discontinuity of the superior glenohumeral ligament (SGHL), presence of biceps tendinopathy, and rotator cuff tears adjacent to the rotator interval. There were 28 pulley lesions noted at arthroscopy. For observers 1, 2, and 3, respectively: MR arthrography showed a sensitivity of 89%, 86%, and 82% and a specificity of 96%, 98%, and 87% in the detection of pulley lesions. Nonvisibility or discontinuity of the SGHL was sensitive (79%, 89%, and 79%) and specific (83%, 79%, and 75%). With the displacement sign, sensitivity was 86%, 82%, and 75% and specificity was 96%, 98%, 90%. Tendinopathy of the LHBT on oblique sagittal images showed a sensitivity of 93%, 82%, 64%; specificity was 81%, 96%, and 85%. Subluxation of the LHBT was insensitive (36%, 50%, and 64%) but specific (100%, 98%, and 96%). MR arthrography is accurate in the detection of pulley lesions; the displacement sign, nonvisibility or discontinuity of the SGHL, and tendinopathy of the LHBT on oblique sagittal images are the most accurate criteria for the detection of pulley lesions.


Global Analysis of 2-Hydroxy Fatty Acids by Gas Chromatography-Tandem Mass Spectrometry Reveals Species-Specific Enrichment in Echinoderms.
Abnormal levels of 2-hydroxy fatty acids (2-OH FAs) are characterized in multiple diseases, and their quantification in foodstuffs is critical to identify the sources of supplementation for potential treatment. However, due to the structural complexity and limited available standards, the comprehensive profiling of 2-OH FAs remains an ongoing challenge. Herein, an innovative approach based on gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed to determine the full profile of these FA metabolites. MS and MS/MS spectra of the trimethylsilyl (TMS) derivatives of 2-OH fatty acid methyl esters (FAMEs) were collected for peak annotation by their signature fragmentation patterns. The structures were further confirmed by validated structure-dependent retention time (RT) prediction models, taking advantage of the correlation between the RT, carbon chain length, and double bond number from commercial standards and pseudostandards identified in the whole-brain samples from mice. An in-house database containing 50 saturated and monounsaturated 2-OH FAs was established, which is expandible when additional molecular species with different chain lengths and backbone structures are identified in the future. A quantitation method was then developed by scheduled multiple reaction monitoring (MRM) and applied to investigate the profiling of 2-OH FAs in echinoderms. Our results revealed that the levels of total 2-OH FAs in sea cucumber Apostichopus japonicas (8.40 ± 0.28 mg/g dry weight) and starfish Asterias amurensis (7.51 ± 0.18 mg/g dry weight) are much higher than that in sea urchin Mesocentrotus nudus (531 ± 108 μg/g dry weight). Moreover, 2-OH C24:1 is the predominant molecular species accounting for 67.9% of the total 2-OH FA in sea cucumber, while 2-OH C16:0 is the major molecular species in starfish. In conclusion, the current innovative GC-MS approach has successfully characterized distinct molecular species of 2-OH FAs that are highly present in sea cucumbers and starfish. Thus, these findings suggest the possibility of developing future feeding strategies for preventing and treating diseases associated with 2-OH FA deficiency.


Postcoital hemoperitoneum caused by ruptured corpus luteal cyst: a hidden etiology.
Corpus luteal rupture is a common gynecologic cause for hemoperitoneum. Recent sexual intercourse is usually a preceding factor. However, postcoital hemoperitoneum without evident vaginal injury or trauma is rarely reported. We present a 34-year-old female who presented to the emergency department with severe bilateral lower quadrant abdominal pain after sexual intercourse. CT of the abdomen and pelvis revealed an intra-abdominal hematoma with extravasation of contrast questionable to be from one of the branches of the left internal iliac artery, and no adnexal abnormalities. Left internal iliac artery angiogram was performed and revealed no active extravasation. Exploratory laparotomy was performed and revealed an actively bleeding left ovarian ruptured area that was repaired and biopsied. No evidence of cysts was observed. Histopathological examination revealed a hemorrhagic corpus luteal cyst. Suspicion for corpus luteal rupture as a cause of postcoital hemoperitoneum should be maintained despite nonevidence of cysts on CT or intraoperatively.


Eczema craquelé as a pointer of internal malignancy--a case report.
A case of eczema craquelé associated with gastric adenocarcinoma is reported. There are localized and generalized forms of eczema craquelé, the generalized forms differing from the localized types because they can be signs of metabolic or internal disease such as cancer. The patterns of the condition are reviewed based on the literature and personal observations.


Impact of obesity in asthma: Possible future therapies.
Obesity is one of the factors associated with the severity of asthma. Obesity is associated with aggravation of the pathophysiology of asthma, including exacerbations, airway inflammation, decreased pulmonary function, and airway hyperresponsiveness. The present review addresses the characteristics of asthma with obesity, focusing especially on the heterogeneity caused by the degree of type 2 inflammation, sex differences, the onset of asthma, and race differences. To understand the severity mechanisms in asthma and obesity, such as corticosteroid resistance, fatty acids, gut microbiome, and cytokines, several basic research studies are evaluated. Finally, possible future therapies, including weight reduction, microbiome-targeted therapies, and other molecular targeted therapies are addressed. We believe that the present review will contribute to better understanding of the severity mechanisms and the establishment of novel treatments for severe asthma patients with obesity.


The prevalence of urinary tract infection in children with severe acute malnutrition: a narrative review.
This article aims to review the current evidence which shows that the prevalence of urinary tract infection (UTI) has been increasing in children with severe acute malnutrition (SAM). UTI remains one of the most common causes of febrile illness in pediatric practice. Most studies conducted among hospitalized children with complicated SAM have reported high prevalence rates of UTI. Clearly, the knowledge of baseline risk of UTI can help clinicians to make informed diagnostic and therapeutic decisions in these children. From the global reports reviewed in this article, UTI prevalence rates range from as low as 6% to as high as 37% in developing countries, while the most common bacterial isolates from urine cultures are Gram-negative coliform organisms such as Escherichia coli and Klebsiella species. These findings form the basis for the current diagnostic and therapeutic guidelines for clinicians managing children with complicated SAM. With the reported high prevalence of UTI among these children and concerns over antibiotic resistance, more extensive data are required using standardized microbiological methods. Thus, the assessment of the performance of urine dipsticks and microscopy against the gold standard urine culture is an important step toward strengthening the evidence for the therapeutic guidelines for UTI in children with SAM.


Self-Assembly of Complex DNA Tessellations by Using Low-Symmetry Multi-arm DNA Tiles.
Modular DNA tile-based self-assembly is a versatile way to engineer basic tessellation patterns on the nanometer scale, but it remains challenging to achieve high levels of structural complexity. We introduce a set of general design principles to create intricate DNA tessellations by employing multi-arm DNA motifs with low symmetry. We achieved two novel Archimedean tiling patterns, (4.8.8) and (126.96.36.199), and one pattern with higher-order structures beyond the complexity observed in Archimedean tiling. Our success in assembling complicated DNA tessellations demonstrates the broad design space of DNA structural motifs, enriching the toolbox of DNA tile-based self-assembly and expanding the complexity boundaries of DNA tile-based tessellation.


The frequency and developmental capability of human embryos containing multinucleated blastomeres.
The frequency of multinucleated blastomeres (MNB) in 2- and 4-cell stage human embryos was recorded immediately before embryo transfer using a high-power inverted microscope. About 44% of patients (150/338) possessed embryos exhibiting MNB. The appearance of this nuclear abnormality was not correlated with maternal age. Overall, 15% of the otherwise good quality embryos (274/1885) that developed after monospermic fertilization contained several multinuclei (from two to seven) in at least one cell. Quite often MNB were found within all cells of the embryo (50% in 2-cell embryos). Blastomere multinucleation was significantly higher in 2-cell than 4-cell embryos (P <0.0001). This suggests that a considerable number of human embryos become abnormal during the first embryonic division. The embryos containing MNB were usually excluded for uterine transfers, with the exception of 19 cases when only such embryos could be replaced (6%; 19/338 patients). The results demonstrated that embryos with MNB may implant (4/19 cases; 21%) and they can lead to both spontaneous abortions and the successful birth of healthy infants (two cases). The fact that in the successful cases, 2-cell stage embryos with a mononucleated and a binucleated blastomere were transferred also suggests that due to the cell totipotency, development of a healthy baby is possible from one normal blastomere. Since multinucleation in early embryos may reflect gross chromosomal abnormalities or development of mosaic embryos, it is advisable not to replace embryos with MNB. Occasional transfers, however, can be considered because defective embryos may sometimes develop normally.


Safe and Effective Implementation of Telestroke in a US Community Hospital Setting.
There is substantial hospital-level variation in use of tissue plasminogen activator (tPA) for treatment of acute ischemic stroke. Telestroke services can bring neurologic expertise to hospitals with fewer resources. To determine whether implementation of a telestroke intervention in a large integrated health system would lead to increased tPA utilization and would change rates of hemorrhagic complications. A stepped-wedge cluster randomized trial of 11 community hospitals connected to 2 tertiary care centers via telestroke, implemented at each hospital incrementally during a 1-year period. We examined pre- and postimplementation data from July 2013 through January 2015. A 2-level mixed-effects logistic regression model accounted for the staggered rollout. Receipt of tPA. Secondary outcome was the rate of significant hemorrhagic complications. Of the 2657 patients, demographic and clinical characteristics were similar in pre- and postintervention cohorts. Utilization of tPA increased from 6.3% before the intervention to 10.9% after the intervention, without a significant change in complication rates. Postintervention patients were more likely to receive tPA than were preintervention patients (odds ratio = 2.0; 95% confidence interval = 1.2-3.4). Before implementation, 8 of the 10 community hospitals were significantly less likely to administer tPA than the highest-volume tertiary care center; however, after implementation, 9 of the 10 were at least as likely to administer tPA as the highest-volume center. Telestroke implementation in a regional integrated health system was safe and effective. Community hospitals' rates of tPA utilization quickly increased and were similar to the largest-volume tertiary care center.


Effects of eggshell temperature and oxygen concentration on embryo growth and metabolism during incubation.
Embryo development and heat production (HP) were studied in eggs of similar size (60 to 65 g) that were incubated at normal (37.8 degrees C) or high (38.9 degrees C) eggshell temperature (EST) and exposed to low (17%), normal (21%), or high (25%) O(2) concentration from d 9 through 19. High EST initially increased HP, but gradually O(2) became more important for HP than EST. Finally,HP was highest for the combination of high EST with high O(2) and lowest for the combination of high EST with low O(2). High EST decreased hatch time, BW, yolk free BW, and relative heart weight. The EST had no effect on residual yolk weight, chick length, or relative liver weight. Increased O(2) increased yolk free BW and chick length and decreased residual yolk weight at hatch. No interactions between EST and O(2) were observed with regard to embryo development and hatchling characteristics. If embryo development is reflected by HP, it can be concluded that high EST primarily increased embryonic development until the second week of incubation. During the third week of incubation, O(2) had a greater effect in determining embryo development than EST.


Suppressing autophagy enhances disulfiram/copper-induced apoptosis in non-small cell lung cancer.
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells. The present study is designed to investigate whether DSF/Cu can induce autophagy in NSCLC cells and to determine the relationship between autophagy and apoptosis. First, we observed that DSF/Cu induced significant cytotoxicity and caspase-dependent apoptosis in NSCLC cells, accompanied by the formation of vacuoles in the cytoplasm. Next, we investigated the levels of autophagic markers, including LC3II (microtubule-associated protein 1 light chain 3), ATG5 and p62 with or without chloroquine by Western blot. In addition, we observed co-localization of LC3 and the lysosomal protein LAMP2 (lysosome-associated membrane protein 2) after treatment with DSF/Cu. The results showed that DSF/Cu induced autophagy. Finally, we demonstrated that DSF/Cu-induced apoptosis was greatly enhanced when autophagy was suppressed with Atg5 siRNA or 3-MA in NSCLC cells. This synergistic effect of DSF/Cu and 3-MA was further confirmed in the NSCLC xenograft model. Taken together, our results show that DSF/Cu stimulates autophagy in NSCLC cells, which is an impediment to DSF/Cu-induced apoptosis.


Immunoregulatory T cells in multiple sclerosis and the effect of interferon beta and glatiramer acetate treatment on T cell subpopulations.
Multiple sclerosis (MS) is a chronic disease characterized by demyelination and chronic inflammation of the central nervous system (CNS). Many of the immune cells including T and B cells seem to be involved in disease pathogenesis by inducing or controlling the immune responses in the nervous system of MS patients. The objective of this study was to evaluate the differences in subpopulations of T cells between MS patients and healthy controls and the effects of interferon beta (INF-beta) and glatiramer acetate (GA) treatment on T cell subpopulations. We have investigated the frequency of subpopulations of T cells using flow cytometry in 84 relapsing-remitting MS patients; forty-five patients started treatment with INF-beta and eighteen patients with GA, twenty-one patients were not treated. We collected blood samples at the beginning and after 6 and 12 months. We observed a significant decrease in CD4(+)CD25(+) Treg cells (p=0.03) and a significant increase in T helper cells (p=0.002) and central memory T cells (p=0.03) in MS patients compared to healthy controls. After INF-beta therapy, we demonstrated a significant increase in naive T cells (p=0.008), a decline in central memory T cells (p=0.01). After GA therapy, we observed a significant increase in naive T cells (p=0.04), a decrease in central memory T cells (p=0.03) and an increase in T-suppressor cells (p=0.008). In conclusion, we demonstrated the imbalance of T-cell subpopulations in MS patients and the potential benefit of DMD (disease modifying drugs) treatment on its restoration.


Statistics of sexual size dimorphism.
In comparative studies of sexual size dimorphism (SSD), the methods used to quantify dimorphism are controversial. SSD is commonly expressed as a ratio between species mean values of males and females, such as M/F or (M-F)/([M+F]/2), but a number of investigators have suggested that ratios should not be used, mainly because their distributions usually violate the assumptions of parametric statistical tests, or because they lead to spurious relationships that invalidate the interpretation and statistical significance of regressions and correlations. As an alternative to ratios, the comparative study of SSD can be conducted by a combination of regression with sex-specific data and residuals from this regression. Twenty-five data sets were selected from the literature and used to duplicate a variety of statistical procedures commonly employed in studies of SSD. All analyses were repeated with five different ratios and with methods that avoid the calculation of any ratios. These data and a review of the statistical properties of ratios and residuals indicate that: (1) most of the ratios used in the SSD literature are unnecessary, and several commonly used ratios are statistically inferior to others. Only two ratios are needed, one on a logarithmic scale and one on a linear scale; (2) there is no problem with spurious correlation or non-normality when ratios are used in several types of statistical procedures commonly employed in studies of SSD; (3) residuals cannot replace ratios for the evaluation of many questions regarding the pattern of SSD among species; and (4) residuals usually are used incorrectly, leading to misspecified regression equations. Most of the questions for which residuals are used should be addressed by multiple regression. These results apply to studies using comparative methods with or without adjustments for phylogenetic effects.


Fate of glyphosate in lakes with varying trophic levels and its modification by root exudates of submerged macrophytes.
Accelerated eutrophication in lakes reduces the number of submerged macrophytes and alters the residues of glyphosate and its degradation products. However, the effects of submerged macrophytes on the fate of glyphosate remain unclear. We investigated eight lakes with varying trophic levels along the middle and lower reaches of the Yangtze River in China, of which five lakes contained either glyphosate or aminomethylphosphate (AMPA). Glyphosate and AMPA residues were significantly positively correlated with the trophic levels of lakes (P < 0.01). In lakes, glyphosate is degraded through the AMPA and sarcosine pathways. Eight shared glyphosate-degrading enzymes and genes were observed in different lake sediments, corresponding to 44 degrading microorganisms. Glyphosate concentrations in sediments were significantly higher in lakes with lower abundances of soxA (sarcosine oxidase) and soxB (sarcosine oxidase) (P < 0.05). In the presence of submerged macrophytes, oxalic and malonic acids secreted by the roots of submerged macrophytes increased the abundance of glyphosate-degrading microorganisms containing soxA or soxB (P < 0.05). These results revealed that a decrease in the number of submerged macrophytes in eutrophic lakes may inhibit glyphosate degradation via the sarcosine pathway, leading to a decrease in glyphosate degradation and an increase in glyphosate residues.


Identification of a Novel Metallo-β-Lactamase, VAM-1, in a Foodborne Vibrio alginolyticus Isolate from China.
A multidrug-resistant Vibrio alginolyticus isolate recovered from a shrimp sample with reduced carbapenem susceptibility produced a novel metallo-β-lactamase (MBL), VAM-1. That carbapenemase shared 67% to 70% amino acid identity with several VMB family subclass B1 MBLs, which were recently reported among some marine bacteria including Vibrio, Glaciecola, and Thalassomonas. The blaVAM-1 gene was located in a novel conjugative plasmid, namely, pC1579, and multiple copies of blaVAM-1 via an unusual mechanism of gene amplification were detected in pC1579. These findings underline the emergence of marine organisms acting as natural reservoirs for MBL genes and the importance of continuous bacterial antibiotic resistance surveillance.


Specificity of an immunofluorescent test for identification of type specific ragweed antibodies.
An immunofluorescent test using ragweed pollen grains for identification of immunolglobulin type-specific rag weed antibodies is described. The test measured effectively antibody specificity produced by immunotherapy with Allpyral. Repeating the test after ragweed inhibition and the use of an unrelated pollen grain verified the specificity of the test.


Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking.
The sinus node is a collection of highly specialised cells constituting the heart's pacemaker. The molecular underpinnings of its pacemaking abilities are debated. Using high-resolution mass spectrometry, we here quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveal significant differences in ion channels responsible for the membrane clock, but not in Ca2+ clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result in pacemaking and a sinus node-like action potential. Combining our quantitative proteomics data with computational modeling, we estimate ion channel copy numbers for sinus node myocytes. Our findings provide detailed insights into the unique molecular make-up of the cardiac pacemaker.


Assembly of Indolenines, 3-Amino Oxindoles, and Aldehydes into Indolenine-Substituted Spiro[pyrrolidin-2,3'-oxindoles] via 1,3-Dipolar Cycloaddition with Divergent Diastereoselectivities.
A novel one-pot 1,3-dipolar cycloaddition of indolenines, 3-aminooxindoles, and aldehydes is reported. The reaction provides indolenine-substituted spiro[pyrrolidin-2,3'-oxindoles] containing four contiguous stereogenic centers in high yields (up to 99%) and excellent diastereoselectivities (up to >20:1 dr) under mild conditions. Remarkably, the inversion of diastereoselectivity could be readily achieved through slightly modifying the reaction conditions.


Evaluating health gains from restorative dental treatment.
A simulation of the caries process over time in posterior approximal tooth surfaces was modelled and tentative evaluations made of health gain from restorative treatment under two sets of assumed conditions. Using published data, the decision model allowed the influence of three variables to be reflected in sensitivity analysis, 1. caries progression, 2. diagnostic accuracy, 3. survival time of fillings. Progress of 50 hypothetical initially sound surfaces, 40 with enamel, and 10 with dentine lesions, was followed over two notional, successive 5-yr time periods. A surface could terminate as sound, enamel lesion, dentine caries, filled, refilled, refilled twice or extracted. Utility values were applied to the end state frequencies to evaluate health gain (from 0 to 100). Under a set of conditions A, diagnostic accuracy reflected that of current general practice and 50% of fillings survived up to 5 yr. Under a set B, diagnostic accuracy was that of a trained epidemiologist and 50% of fillings survived up to 10 yr. Assumption A scored 75.3 while B scored 81.9, suggesting scope for added health gain through improvement of practice standards.


Worms and bugs of the gut: the search for diagnostic signatures using barcoding, and metagenomics-metabolomics.
Gastrointestinal (GI) helminth infections cause significant morbidity in both humans and animals worldwide. Specific and sensitive diagnosis is central to the surveillance of such infections and to determine the effectiveness of treatment strategies used to control them. In this article, we: (i) assess the strengths and limitations of existing methods applied to the diagnosis of GI helminth infections of humans and livestock; (ii) examine high-throughput sequencing approaches, such as targeted molecular barcoding and shotgun sequencing, as tools to define the taxonomic composition of helminth infections; and (iii) discuss the current understanding of the interactions between helminths and microbiota in the host gut. Stool-based diagnostics are likely to serve as an important tool well into the future; improved diagnostics of helminths and their environment in the gut may assist the identification of biomarkers with the potential to define the health/disease status of individuals and populations, and to identify existing or emerging anthelmintic resistance.


Association of IL-8 (-251 a/t) gene polymorphism with clinical parameters and chronic periodontitis.
To investigate the correlation between IL-8 (-251 A/T) gene polymorphism and susceptibility to chronic periodontitis as well as different clinical parameters and severity of the condition in patients referred to dental school, Shiraz University of Medical Sciences, Shiraz, Iran. In this randomized cross sectional study, 227 non-smoking patients with chronic periodontitis (test) and 40 healthy individuals (control) were enrolled in this experiment and the following clinical parameters were employed in the study: Periodontal Pocket Depth (PPD), Clinical Attachment Level (CAL) and Bone Loss (BL). All participants underwent the PCR (Polymerase Chain Reaction) test to detect 251 A/T Single Nucleotide Polymorphism of IL8 gene. No significant correlation was perceived between different genotypes of IL-8 and the severity of the periodontal condition (P= 0.164), neither did we detect any substantial association between different IL-8 genotypes and the mean PPD (P=0.525), CAL (P=0.151), BL (P=0.255), PI (P=0.087), BOP (P=0.265) and the average number of teeth (P=0.931). The results implied that there was no explicit correlation between 251 (A/T) IL-8 gene polymorphism and the severity of the chronic periodontal disease or to the susceptibility to it.


Posttranslational modifications of NEMO and its partners in NF-kappaB signaling.
NEMO, the regulatory subunit of the IkappaB kinase (IKK) complex that controls the activation of the transcription factor NF-kappaB, is required for IKK function in most situations, but its exact mode of action has remained elusive until recently. A series of publications now provides information about how posttranscriptional modifications of NEMO, such as ubiquitination, sumoylation or phosphorylation, regulate its function in the IKK complex. These modifications might also regulate a cytosolic pool of free NEMO that controls the activation of NF-kappaB induced by genotoxic stress. Together with a better identification of the modifications controlling partners of NEMO, a clearer picture of how IKK becomes activated upon cell stimulation is starting to emerge, providing new clues for how the NF-kappaB pathway could be modulated for therapeutic purposes.


Hydrogen-bonding-induced polymorphous phase transitions in 2D organic nanostructures.
The 2D self-assembly of various 2-hydroxy-7-alkoxy-9-fluorenone (HAF) molecules has been investigated by scanning tunneling microscopy (STM) at the liquid/solid interface. A systematic study revealed that HAF molecules with different numbers of carbon atoms in their alkoxy chains could form two or three different kinds of nanostructures, that is, less-ordered, flower-like, and zig-zag patterns, owing to the formation of different types of intermolecular hydrogen bonds. The observed structural transition was found to be driven by molecular thermodynamics, surface diffusion, and the voltage pulse that was applied to the STM tip. The zig-zag pattern was the most stable of these configurations. An odd-even effect on the flower-like structure, as induced by the odd and even number of carbon atoms in the side chain, was observed by STM. The influence of the odd-even effect on the melting point has a close relationship with the molecular self-assembled pattern. Our results are significant for understanding the influence of hydrogen-bonding interactions on the dominant adsorption behavior on the surface and provide a new visual approach for observing the influence of the odd-even effect on the phase transition.


Evaluation of Zebrafish Toxicology and Biomedical Potential of Aeromonas hydrophila Mediated Copper Sulfide Nanoparticles.
The present study deals with extracellular synthesis and characterization of copper sulfide (CuS) nanoparticles using Aeromonas hydrophila, and the biological applications of the synthesized CuS like antibacterial, anti-inflammatory, and antioxidant activity were reported. Further, the toxicological effects of the CuS were evaluated using zebrafish as an animal model. The primary step of the synthesis was carried out by adding the precursor copper sulfates to the culture supernatant of Aeromonas hydrophila. The UV-visible spectrophotometer was used to characterize the synthesized nanoparticles, and the peak was obtained at 307 nm through the reduction process. Fourier transform infrared spectroscopy (FTIR) was involved to find out the functional groups (carboxylic acid, alcohols, alkanes, and nitro compounds) associated with copper sulfide nanoparticles (CuS-NPs). Atomic force microscopy (AFM) was used to characterize the CuS topographically, and a scanning electron microscope (SEM) revealed about 200 nm sized CuS nanoparticles with agglomerated structures. Overall, the characterized nanoparticles can be considered as a potential candidate with therapeutic proficiencies as antibacterial, antioxidant, and anti-inflammatory mediator/agents.


[A review on the water physiological characteristics of Tamarix and its prospect].
It is very important to study and grasp the water physiological characteristics of Tamarix in order to use properly and scientifically manage it. Based on the multiply studies on the water physiological characteristics of Tamarix (P-V curves, predawn water potential and water potential daily course and transpiration rate) for many years, a preliminary comment was given on the experimental methods used at home and abroad. The aims of this paper is to understand the ecological characteristics of Tamarix as fast as possible and provide theoretical bases for the restoration and re-establishment of Tamarix in the arid and semi-arid region.


Sustaining and Expanding Telehealth: A Survey of Business Models from Selected Prominent U.S. Telehealth Centers.
Telehealth centers across the country, including our own center, are addressing sustainability and best practice business models. We undertook this survey to explore the business models being used at other established telehealth centers. In the literature on telehealth and sustainability, there is a paucity of comparative studies as to how successful telehealth centers function. In this study, we compared the business models of 10 successful telehealth centers. We conducted the study by interviewing key individuals at the centers, either through teleconference or telephone. We found that there are five general approaches to sustaining a telehealth center: grants, telehealth network membership fees, income from providing clinical services, per encounter charges, and operating as a cost center. We also found that most centers use more than one approach. We concluded that, although the first four approaches can contribute to the success of a center, telehealth centers are and should remain cost centers for their respective institutions.


Spatial learning by rats across visually disconnected environments.
Two spatial tasks were designed to test specific properties of spatial representation in rats. In the first task, rats were trained to locate an escape hole at a fixed position in a visually homogeneous arena. This arena was connected with a periphery where a full view of the room environment existed. Therefore, rats were dependent on their memory trace of the previous position in the periphery to discriminate a position within the central region. Under these experimental conditions, the test animals showed a significant discrimination of the training position without a specific local view. In the second task, rats were trained in a radial maze consisting of tunnels that were transparent at their distal ends only. Because the central part of the maze was non-transparent, rats had to plan and execute appropriate trajectories without specific visual feedback from the environment. This situation was intended to encourage the reliance on prospective memory of the non-visited arms in selecting the following move. Our results show that acquisition performance was only slightly decreased compared to that shown in a completely transparent maze and considerably higher than in a translucent maze or in darkness. These two series of experiments indicate (1) that rats can learn about the relative position of different places with no common visual panorama, and (2) that they are able to plan and execute a sequence of visits to several places without direct visual feed-back about their relative position.


SRSF7 knockdown promotes apoptosis of colon and lung cancer cells.
Serine/arginine-rich (SR) proteins are a family of important splicing factors, which are involved in multiple aspects of RNA processing, including splicing, mRNA nuclear export, mRNA stability and translation. Previous studies have identified a number of SR proteins that exhibit abnormal expression in various tumor types. In the present study, the expression and function of serine/arginine-rich splicing factor 7 (SRSF7) were investigated in colon and lung cancer. Using tissue immunohistochemistry, it was observed that SRSF7 was overexpressed in colon and lung cancer tissues. As the role of SRSF7 in cancer remains to be fully elucidated, the expression of SRSF7 was knocked down in the present study by transfecting SRSF7-specific small interfering RNAs (siRNAs) into the HCT116 colon cancer cell line and A549 lung cancer cell line, which exhibited elevated expression of SRSF7. MTS assays, western blot analysis, flow cytometry and spectrofluorometer analyses were performed to assess the effects of SRSF7 knockdown on the proliferation and apoptosis of cells. The results demonstrated that the expression of SRSF7 was efficiently knocked down by SRSF7 siRNA, and that SRSF7 knockdown inhibited proliferation and enhanced apoptosis of HCT116 and A549 cells. Further experiments involving BEAS-2B cells stably overexpressing SRSF7, and A549 cells with stable knockdown of SRSF7 revealed that SRSF7 regulated the splicing of the apoptosis regulator Fas. Collectively, these data indicated that SRSF7 is critical for the survival of colon and lung cancer cells, and may be a potential therapeutic target for the treatment of colon and lung cancer.


Persistence in metabolic nets.
In an attempt to improve the understanding of complex metabolic dynamic phenomena, we have analysed several 'metabolic networks', dynamical systems which, under a single formulation, take into account the activity of several catalytic dissipative structures, interconnected by substrate fluxes and regulatory signals. These metabolic networks exhibit a rich variety of self-organized dynamic patterns, with e.g., phase transitions emerging in the whole activity of each network. We apply Hurst's R/S analysis to several time series generated by these metabolic networks, and measure Hurst exponents H < 0.5 in most cases. This value of H, indicative of antipersistent processes, is detected at very high significance levels, estimated with detailed Monte Carlo simulations. These results show clearly the considered type of metabolic networks exhibit long-term memory phenomena.


New Findings in Prunus padus L. Fruits as a Source of Natural Compounds: Characterization of Metabolite Profiles and Preliminary Evaluation of Antioxidant Activity.
European bird cherry (Prunus padus L.) has been known since the Middle Ages for its medical/food use and high health-promoting value. This study aimed to assess the potential of these fruits as a source of bioactive compounds through the characterization of its physicochemical traits, nutraceutical properties, phytochemical composition via HPLC fingerprint, and antioxidant capacity. Fully ripened fruits of Prunus padus L. (Colorata cv) were collected in mid-July 2017 in Chieri, north-western Italy. The TPC (194.22 ± 32.83 mgGAE/100 gFW) and TAC (147.42 ± 0.58 mgC3G/100 gFW) values were obtained from the analyzed extracts. The most important phytochemical class was organic acids (48.62 ± 2.31%), followed by polyphenols (35.34 ± 1.80%), monoterpenes (9.36 ± 0.64%), and vitamin C (6.68 ± 0.22%). In this research the most important flavonols selected as marker were quercitrin (16.37 ± 3.51 mg/100 gFW) and quercetin (11.86 ± 2.36 mg/100 gFW). Data were reported based on fresh weight. Moreover, fresh fruits showed a mean antioxidant activity value of 17.78 ± 0.84 mmol Fe2+·kg-1. Even though the seeds and leaves contain cyanogenic glycosides, this study showed that these fruits could be a natural source of bioactive compounds with high antioxidant properties, due to the contents of organic and phenolic acids, catechins, and a synergetic effect of vitamin C and flavonoids.


Rab3D and annexin A2 play a role in regulated secretion of vWF, but not tPA, from endothelial cells.
von-Willebrand factor (vWF) and tissue-type plasminogen activator (tPA) are products of endothelial cells acutely released into the vasculature following cell activation. Both factors are secreted after intraendothelial Ca2+ mobilization, but exhibit opposing physiological effects with vWF inducing coagulation and tPA triggering fibrinolysis. To identify components that could regulate differentially the release of pro- and antithrombogenic factors, we analyzed the contribution of Rab3D and the annexin A2/S100A10 complex, proteins implicated in exocytotic events in other systems. We show that mutant Rab3D proteins interfere with the formation of bona fide Weibel-Palade bodies (WPbs), the principal storage granules of multimeric vWF, and consequently the acute, histamine-induced release of vWF. In contrast, neither appearance nor exocytosis of tPA storage granules is affected. siRNA-mediated downregulation of annexin A2/S100A10 and disruption of the complex by microinjection of peptide competitors result in a marked reduction in vWF but not tPA secretion, without affecting the appearance of WPbs. This indicates that distinct mechanisms underlie the acute secretion of vWF and tPA, enabling endothelial cells to fine-regulate the release of thrombogenic and fibrinolytic factors.


Novel prognostic scoring system for diffuse large B-cell lymphoma.
The objective of the present study was to evaluate the prognostic values of platelet count (PLT) and platelet to lymphocyte ratio (PLR) in diffuse large B-cell lymphoma (DLBCL), creating a novel prognostic scoring system. A total of 309 patients with newly diagnosed DLBCL were retrospectively analyzed. Receiver operating characteristic analysis was used to determine the optimal threshold values for PLT and PLR, which were 250×109/l and 170, respectively. The patients with PLT ≥250×109/l and PLR ≥170 experienced significantly decreased overall survival (OS) (P<0.001) and progression-free survival (PFS) times (P=0.003, P<0.001) In multivariate analysis, PLR was a significant prognostic factor for OS (P<0.001) and PFS (P=0.003) time, whereas PLT was not a risk factor for PFS or OS time. According to the results of Cox regression analysis, a novel prognostic scoring system was created that combined PLR and β2-microglobulin level with International Prognostic Index value or age-adjusted International Prognostic Index value and the patients were divided into three groups: i) Low-risk patients with a PLR <170, International Prognostic Index (IPI) <2 scores or age-adjusted International Prognostic Index (aaIPI)=0 and normal β2m; ii) high-risk patients with a PLR ≥170, IPI ≥4 or aaIPI=3 and high level of β2m; and iii) intermediate-risk patients. The novel score predicted 5-year OS rates of 86.4, 54.1 and 21.1% in the low-, intermediate- and high-risk groups, respectively (P<0.001). This novel prognostic scoring system may aid the evaluation of patient prognosis and guide treatment.


Characteristics of W Doped Nanocrystalline Carbon Films Prepared by Unbalanced Magnetron Sputtering.
Nanocrystalline tungsten doped carbon (WC) films were prepared by unbalanced magnetron sputtering. Tungsten was used as the doping material in carbon thin films with the aim of application as a contact strip in an electric railway. The structural, physical, and electrical properties of the fabricated WC films with various DC bias voltages were investigated. The films had a uniform and smooth surface. Hardness and frication characteristics of the films were improved, and the resistivity and sheet resistance decreased with increasing negative DC bias voltage. These results are associated with the nanocrystalline WC phase and sp(2) clusters in carbon networks increased by ion bombardment enhanced with increasing DC bias voltage. Consequently, the increase of sp(2) clusters containing WC nanocrystalline in the carbon films is attributed to the improvement in the physical and electrical properties.


Generating Nonmosaic Mutants in Xenopus Using CRISPR-Cas in Oocytes.
In CRISPR-Cas9 genome editing, double-strand DNA breaks (DSBs) primarily undergo repair through nonhomologous end joining (NHEJ), which produces insertion or deletion of random nucleotides within the targeted region (indels). As a result, frameshift mutation-mediated loss-of-function mutants are frequently produced. An alternative repair mechanism, homology-directed repair (HDR), can be used to fix DSBs at relatively low frequency. By injecting a DNA-homology repair construct with the CRISPR-Cas components, specific nucleotide sequences can be introduced within the target region by HDR. We have taken advantage of the fact that Xenopus oocytes have much higher levels of HDR than eggs to increase the effectiveness of creating precise mutations. We introduced the oocyte host transfer technique, well established for knockdown of maternal mRNA for loss-of-function experiments, to CRISPR-Cas9-mediated genome editing. The host-transfer technique is based on the ability of Xenopus oocytes to be isolated, injected with CRISPR-Cas components, and cultured in vitro for up to 5 d before fertilization. During these 5 d, CRISPR-Cas components degrade, preventing further alterations to the paternal or maternal genomes after fertilization and resulting in heterozygous, nonmosaic embryos. Treatment of oocytes with a DNA ligase IV inhibitor, which blocks the NHEJ repair pathway, before fertilization further improves the efficiency of HDR. This method allows straightforward generation of either nonmosaic F0 heterozygous indel mutant Xenopus or Xenopus with efficient, targeted insertion of small DNA fragments (73-104 nt). The germline transmission of mutations in these animals allows homozygous mutants to be obtained one generation (F1) sooner than previously reported.


Information Transfer Capacity of Articulators in American Sign Language.
The ability to convey information is a fundamental property of communicative signals. For sign languages, which are overtly produced with multiple, completely visible articulators, the question arises as to how the various channels co-ordinate and interact with each other. We analyze motion capture data of American Sign Language (ASL) narratives, and show that the capacity of information throughput, mathematically defined, is highest on the dominant hand (DH). We further demonstrate that information transfer capacity is also significant for the non-dominant hand (NDH), and the head channel too, as compared to control channels (ankles). We discuss both redundancy and independence in articulator motion in sign language, and argue that the NDH and the head articulators contribute to the overall information transfer capacity, indicating that they are neither completely redundant to, nor completely independent of, the DH.


Stress, symptoms, self-monitoring confidence, well-being, and social support in the progression of preeclampsia/gestational hypertension.
To investigate the relationships of psychological stress, preeclampsia/gestational hypertension symptoms, confidence in self-monitoring, well-being, and perceived social support with preeclampsia/gestational hypertension disease progression in outpatient women. Women with mild and severe preeclampsia/gestational hypertension were compared for differences in these variables. A retrospective, correlational, and comparative design. Postpartum units of three urban hospitals in Philadelphia, Pennsylvania. One hundred postpartum women with preeclampsia/gestational hypertension. Psychological stress measured by the Perceived Stress Scale, preeclampsia/gestational hypertension symptoms by the Preeclampsia/Gestational Hypertension Checklist, confidence in self-monitoring by the Self-Confidence in Self-Monitoring Scale, well-being by the Index of Well-Being, and social support by the Interpersonal Support Evaluation List. Women with worsening/severe preeclampsia/gestational hypertension reported a significantly higher number of symptoms than women with mild preeclampsia/gestational hypertension (p= .02). Psychological stress was significantly higher (p= .04) in women with worsening/severe preeclampsia/gestational hypertension. There were no differences in well-being, self-confidence in self-monitoring, or perceived social support between women with mild preeclampsia/gestational hypertension and those with worsening preeclampsia/gestational hypertension. Worsening/severe preeclampsia/gestational hypertension was associated with increasing psychological stress and a higher number of preeclampsia/gestational hypertension symptoms.


PROM1 and CTGF Expression in Childhood MLL-Rearrangement Acute Lymphoblastic Leukemia.
The prognosis of over 90% of infant acute lymphoblastic leukemia (ALL) remains poor because of harboring the mixed-lineage leukemia gene (MLL) fusion. To give insight into the critical coexpressed genes related to the MLL-rearrangement (MLL-R) gene in childhood acute lymphoblastic leukemia, we integrated different bioinformatic methods. First, the gene expression data of MLL-R ALL and normal samples from GSE13159 and GSE13164 were analyzed using "compare" function in the Oncomine database. The top 150 overexpressed and 150 underexpressed genes were identified by the Oncomine website. Then, we employed the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) to define functional genes for the 300 DEGs. The Cytoscape identified two important networks for overexpressed genes, including 35 functional genes, among which PROM1, FLT3, CTGF, LGALS1, IGFBP7, ZNRF1, and RUNX2 were considered as the key genes because of their high expression in MLL-R ALL compared to the expression in other subclassification of leukemia in the MILE dataset. Further analysis of GSE68720, GSE19475, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL (phase I) database confirmed the robust expression of 7 key genes in MLL-R compared to MLL-germline (MLL-G) childhood ALL. Kaplan-Meier analysis indicated that childhood ALL patients with high PROM1 and CTGF expression had significantly poor overall survival. These findings suggest that PROM1 and CTGF represent two potential therapeutic targets for childhood MLL-R ALL.


Identification of Novel Physiological Substrates of Mycobacterium bovis BCG Protein Kinase G (PknG) by Label-free Quantitative Phosphoproteomics.
Mycobacterial Ser/Thr kinases play a critical role in bacterial physiology and pathogenesis. Linking kinases to the substrates they phosphorylate in vivo, thereby elucidating their exact functions, is still a challenge. The aim of this work was to associate protein phosphorylation in mycobacteria with important subsequent macro cellular events by identifying the physiological substrates of PknG in Mycobacterium bovis BCG. The study compared the phosphoproteome dynamics during the batch growth of M. bovis BCG versus the respective PknG knock-out mutant (ΔPknG-BCG) strains. We employed TiO2 phosphopeptide enrichment techniques combined with label-free quantitative phosphoproteomics workflow on LC-MS/MS. The comprehensive analysis of label-free data identified 603 phosphopeptides on 307 phosphoproteins with high confidence. Fifty-five phosphopeptides were differentially phosphorylated, of these, 23 phosphopeptides were phosphorylated in M. bovis BCG wild-type only and not in the mutant. These were further validated through targeted mass spectrometry assays (PRMs). Kinase-peptide docking studies based on a published crystal structure of PknG in complex with GarA revealed that the majority of identified phosphosites presented docking scores close to that seen in previously described PknG substrates, GarA, and ribosomal protein L13. Six out of the 22 phosphoproteins had higher docking scores than GarA, consistent with the proteins identified here being true PknG substrates. Based on protein functional analysis of the PknG substrates identified, this study confirms that PknG plays an important regulatory role in mycobacterial metabolism, through phosphorylation of ATP binding proteins and enzymes in the TCA cycle. This work also reinforces PknG's regulation of protein translation and folding machinery.


The effects of sclerotherapy with 5% trichloroacetic acid on the cyst diameter and ovarian tissue in the rat ovarian cyst model.
The aim of this study was to compare the effects of only aspiration with aspiration and 5% trichloroacetic acid (TCA) application on ovarian cyst size and ovarian reserve. The ovarian cysts of 14 rats that were divided into two groups randomly were investigated after total salpingectomy procedure. G1 was the group of saline application after cyst aspiration, while in G2, after aspiration 5% TCA at half amount of aspiration volume was injected into the cyst and re-aspirated after five minutes. The abdomens of the rats were closed and re-explored after 1 month. The cyst diameters of the rats in each group were measured. Ovaries were removed for histopathological examination. There was no significant difference in cyst diameter in G1 before and after aspiration. In G2, there was a significant decrease in cyst size after TCA application. Ovarian follicle counts were not significantly different between the two groups. In conclusion, application of 5% TCA to the ovarian cysts for five minutes significantly reduces the cyst size. Impact Statement What is already known on this subject: Minimally invasive therapies come into prominence to avoid surgical complications and diminished fertility in the treatment of ovarian cysts. USG-guided aspiration and sclerosis has been reported as cost-efficient and effective treatment methods for localised benign cysts in other organs such as the thyroid, parathyroid, liver, kidney and spleen. It has been shown that sclerotherapy applied to infertile women with ovarian cysts reduces pelvic pain without affecting the number of follicles, term pregnancy and abortion rates, extracted oocytes, embryo quality or hormonal levels when compared to non-ovarian cystic infertile women. TCA is a chemical agent that is topically applied, not systemically absorptive, which causes denaturation of proteins and structural cell death, resulting in coagulation necrosis after chemical cauterisation. For this reason, we used 5% TCA to treat simple ovarian cysts on a rat model. What the results of this study add: In this experimental study, we showed that the application of 5% TCA into the cyst for five minutes - then aspirated - significantly reduced the size of the ovarian cysts. Five percent TCA application did not affect the ovarian reserve. What the implications are of these findings for clinical practice and/or further research: Our study is original because of the fact that to the best of our knowledge, this is the first study about the use of 5% TCA in treatment of ovarian cysts in the literature.


The serum complement system: a simplified laboratory exercise to measure the activity of an important component of the immune system.
The immune system is a vital physiological component that affords animals protection from disease and is composed of innate and adaptive mechanisms that rely on cellular and dissolved components. The serum complement system is a series of dissolved proteins that protect against a variety of pathogens. The activity of complement in serum can be determined by its ability to lyse red blood cells in vitro. Here, we describe a modification of a standard complement hemolysis assay that makes an interesting and informative laboratory exercise suitable for a variety of courses including physiology.


Wheat PR-1 proteins are targeted by necrotrophic pathogen effector proteins.
Recent studies have identified that proteinaceous effectors secreted by Parastagonospora nodorum are required to cause disease on wheat. These effectors interact in a gene-for-gene manner with host-dominant susceptibilty loci, resulting in disease. However, whilst the requirement of these effectors for infection is clear, their mechanisms of action remain poorly understood. A yeast-two-hybrid library approach was used to search for wheat proteins that interacted with the necrotrophic effector SnTox3. Using this strategy we indentified an interaction between SnTox3 and the wheat pathogenicity-related protein TaPR-1-1, and confirmed it by in-planta co-immunprecipitation. PR-1 proteins represent a large family (23 in wheat) of proteins that are upregulated early in the defence response; however, their function remains ellusive. Interestingly, the P. nodorum effector SnToxA has recently been shown to interact specifically with TaPR-1-5. Our analysis of the SnTox3-TaPR-1 interaction demonstrated that SnTox3 can interact with a broader range of TaPR-1 proteins. Based on these data we utilised homology modeling to predict, and validate, regions on TaPR-1 proteins that are likely to be involved in the SnTox3 interaction. Precipitating from this work, we identified that a PR-1-derived defence signalling peptide from the C-terminus of TaPR-1-1, known as CAPE1, enhanced the infection of wheat by P. nodorum in an SnTox3-dependent manner, but played no role in ToxA-mediated disease. Collectively, our data suggest that P. nodorum has evolved unique effectors that target a common host-protein involved in host defence, albeit with different mechanisms and potentially outcomes.


Roadblocks in education amidst global crisis-A study based in India.
The outbreak of the COVID-19 pandemic compelled the closure of educational institutions and forced students to complete nearly two years of schooling online, impacting their physical and emotional development tremendously. This exploratory study investigates the wide-ranging impact of online education on Indian students during the COVID-19 pandemic and discusses the challenges exacerbated by disparities in access to digital devices and reliable internet service. The paper also focuses on the physical and mental health issues that arose in student cohorts as a result of the abrupt shift to online learning, and investigates the relationship between students' socioeconomic status and the nature and frequency of health issues experienced by them. A total of 832 respondents completed a 40-item survey that was administered online and through interviews. The paper analysed the impact of access to digital resources and teachers' training in information and communication technology on the perception of the quality of education provided by the institutions. We further analysed the impact of the adoption of online educational platforms on students' mental and physical health. The study found a positive relationship between the number of hours spent online, and the physical and mental health issues experienced by students. Participants reported an overall higher perception of stress and anxiety, loss of concentration, and dissatisfaction with the quality of education. Our data suggest that COVID-19 has exacerbated the digital divide. Urgent investments are needed to provide universal access to reliable internet services, and to develop a pedagogy that supports an agile and adaptable educational system, capable of providing effective learning and evaluation, while supporting students' physical and mental health.


Association of Nat2 Gene Polymorphism with Antitubercular Drug-induced Hepatotoxicity in the Eastern Uttar Pradesh Population.
Introduction Tuberculosis (TB) remains an important cause of morbidity and mortality worldwide. There are more than 20 drugs available for TB treatment. Hepatotoxicity is the most serious adverse drug reaction of anti-TB drugs. Various pathogenesis and genetic factors are associated with antituberculosis drug-induced hepatotoxicity (ATDIH). Antituberculosis drugs (ATDs) are mostly metabolized by N-acetyltransferase 2 (NAT2). Therefore, in this study, we aim to evaluate the role of the NAT2 genotype in ATDIH in the eastern Uttar Pradesh population. Methods A total of 100 TB patients who had been treated with anti-TB drugs were enrolled in this studied. In this group, 70 TB patients did not develop drug-induced hepatotoxicity (tolerant control group) and 30 TB patients developed ATDIH (ATDIH group). The genetic polymorphisms of the NAT2 genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype and allele frequencies were evaluated by the t-test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results There is a high percentage of slow acetylators in the Eastern Uttar Pradesh population. Four percent of people are fast acetylators, 34% are intermediate acetylators, and 62% are slow acetylators. The frequency of slow acetylators in the NAT2 genotype was commonly present and was not significantly different between the ATDIH (73.33%) and tolerant control groups (61.40%). However, the genotypic distribution of variants of slow-acetylator genotypes (NAT2*6/7, NAT2*5/7, and NAT2*5/6) was also not significantly different in ATDIH. Conclusion In the present study, the slow acetylators of the NAT2 genotype did not contribute to the elevated risk of ATDIH development in tuberculosis patients.


Ultrastructural localization of a neutral and basic amino acid transporter in rat kidney and intestine.
A sodium-independent neutral and basic amino acid transporter (NBAT) from rat kidney was recently cloned and its amino acid sequence deduced. We used light and electron microscopic immunoperoxidase labeling to determine the cellular localization of NBAT in rat kidney and small intestine. The localization was carried out using site-directed antisera raised against synthetic peptides within NBAT. The most prominent localization of NBAT was in microvilli of epithelial cells lining renal proximal tubules. Microvilli of small intestinal epithelia were less frequently immunoreactive. Unexpectedly, the most intense labeling in the small intestine was seen within enteroendocrine cells and submucosal neurons. The neuronal labeling was highly localized within dense core vesicles in axon terminals apposed to the basal lamina near fenestrated blood vessels. These results support the proposal that NBAT plays a role in reabsorption of amino acids in renal tubules. In addition, they suggest that NBAT (or NBAT-like proteins) may have multiple functions in the small intestine, including luminal uptake of amino acids and vesicular uptake of related substrates into enteroendocrine cells and enteric neurons.


[A case of gastric mucosal laceration due to seat belt injury].
A 69-year-old man was involved in a road traffic accident wherein his car hit a telegraph pole and turned over. He reported wearing a seatbelt and denied any injuries or pain at that time. Six hours after the accident, however, he developed melena and hematemesis. Computed tomography performed on admission to our hospital revealed no evidence of traumatic pneumothorax, intra-abdominal bleeding, or pneumoperitoneum. However, there was evidence of contrast medium leakage from the stomach. Emergency endoscopy revealed a mucosal laceration on the lesser curvature in the cardiac region, with evidence of arterial hemorrhage from visible vessels. Hemostasis was achieved endoscopically by injection of hypertonic saline-epinephrine and clipping. Endoscopic treatment of gastric injury following blunt abdominal trauma is rare. Here we report a case and present a review of the relevant literature.


Dynamics of the acetylcholine receptor pore at the gating transition state.
Neuromuscular acetylcholine receptors (AChRs) are ion channels that alternatively adopt stable conformations that either allow (open) or prohibit (closed) ionic conduction. We probed the dynamics of pore (M2) residues at the diliganded gating transition state by using single-channel kinetic and rate-equilibrium free energy relationship (phi-value) analyses of mutant AChRs. The mutations were at the equatorial (9') position of the alpha, beta, and epsilon subunits (n = 15) or at sites between the equator and the extracellular domain in the alpha-subunit (n = 8). We also studied AChRs having only one of the two alpha-subunits mutated. The results indicate that the alpha-subunit, like the delta-subunit, has a region of flexure near the middle of M2, that the two alpha-subunits experience distinct energy barriers to gating at the equator (but not elsewhere), and that the collective subunit motions at the equator are asymmetric during the AChR gating isomerization.


Cold stimuli evoke potentials that can be recorded directly from parasylvian cortex in humans.
Anatomic, imaging, and lesion studies suggest that insular or parietal opercular cortical structures mediate the sensation of nonpainful cold. We have now tested the hypothesis that cold stimuli evoke electrical responses from these cortical structures in humans. We recorded the response to cold stimuli from electrodes implanted directly over parasylvian cortex for the investigation of intractable seizures. The results demonstrate that slow potentials can be evoked consistently over structures adjacent to the sylvian fissure in response to nonpainful cold. The polarity of these cold evoked potentials (EPs) for electrodes above the sylvian fissure is opposite to those below. These results suggest that the generator of cold EPs is close to the sylvian fissure in the parietal operculum or insula.


CO-Releasing Molecule (CORM)-3 Ameliorates Spinal Cord-Blood Barrier Disruption Following Injury to the Spinal Cord.
Spinal cord injury (SCI) is a clinical tough neurological problem without efficient cure currently. Blood-spinal cord barrier (BSCB) interruption is not only a crucial pathological feature for SCI process but is a possible target for future SCI treatments; however, few treatments have been developed to intervene BSCB. In the present study, we intravenously injected CO-releasing molecule3 (CORM-3), a classical exogenous CO donor, to the rats experiencing SCI and assessed its protection on BSCB integrity in rats. Our results demonstrated that the exogenous increasing of CO by CORM-3 blocked the tight junction (TJ) protein degeneration and neutrophils infiltration, subsequently suppressed the BSCB damage and improved the motor recovery after SCI. And we certified that the CO-induced down-regulation of MMP-9 expression and activity in neutrophil might be associated with the NF-κB signaling. Taken together, our study indicates that CO-releasing molecule (CORM)-3 ameliorates BSCB after spinal cord injury.


Identification with the American South and Anti-Muslim Attitudes.
The number of anti-Muslim hate groups in the U.S. nearly tripled between 2015 and 2016. In addition, the number of hate crimes committed against members of the religion jumped 67% in 2015 alone. Addressing the rise in anti-Muslim prejudice is critical. We examined (N = 406) the role of regional identification in predicting anti-Muslim attitudes. That is, identification with the American South, a more conservative and religious part of the country with a history of slavery and violent secession movements, predicted anti-Muslim attitudes. This relationship was mediated by conservation values. For Southerners who strongly identified with "the South", the endorsement of values related to a general resistance to change led to greater anti-Muslim attitudes. Anti-Muslim bias may lie in perceptions of threat: for strongly identified Southerners, the Muslim faith is viewed as a societal threat.


Crystallization and Organic Field-Effect Transistor Performance of a Hydrogen-Bonded Quaterthiophene.
Crystalline thin films of π-conjugated molecules are relevant as the active layers in organic electronic devices. Therefore, materials with enhanced control over the supramolecular arrangement, crystallinity, and thin-film morphology are desirable. Herein, it is reported that hydrogen-bonded substituents serve as additional structure-directing elements that positively affect crystallization, thin-film morphology, and device performance of p-type organic semiconductors. It is observed that a quaterthiophene diacetamide exhibits a denser packing than that of other quaterthiophenes in the single-crystal structure and, as a result, displays enhanced intermolecular electronic interactions. This feature was preserved in crystalline thin films that exhibited a layer-by-layer morphology, with large domain sizes and high internal order. As a result, organic field-effect transistors of these polycrystalline thin films showed mobilities in the range of the best mobility values reported for single-crystalline quaterthiophenes. The use of hydrogen-bonded groups may, thus, provide an avenue for organic semiconducting materials with improved morphology and performance.


Proteomics analysis reveals the molecular mechanism underlying the transition from primary to secondary growth of poplar.
Wood is the most important natural source of energy and also provides fuel and fiber. Considering the significant role of wood, it is critical to understand how wood is formed. Integration of knowledge about wood development at the cellular and molecular levels will allow more comprehensive understanding of this complex process. In the present study, we used a comparative proteomic approach to investigate the differences in protein profiles between primary and secondary growth in young poplar stems using tandem mass tag (TMT)-labeling. More than 10,816 proteins were identified, and, among these, 3106 proteins were differentially expressed during primary to secondary growth. Proteomic data were validated using a combination of histochemical staining, enzyme activity assays, and quantitative real-time PCR. Bioinformatics analysis revealed that these differentially expressed proteins are related to various metabolic pathways, mainly including signaling, phytohormones, cell cycle, cell wall, secondary metabolism, carbohydrate and energy metabolism, and protein metabolism as well as redox and stress pathways. This large proteomics dataset will be valuable for uncovering the molecular changes occurring during the transition from primary to secondary growth. Further, it provides new and accurate information for tree breeding to modify wood properties.


[Effect of lithium preparations on cardiac arrhythmias resulting from ligation of the common carotid arteries].
In experiments on cats with dissected vagus and aortal nerves under chloralose-urethane anesthesia, ventricular disorders of the cardiac rhythm were induced by ligation of the common carotid arteries. Appearance of arrhythmias was preceded by an increase in the sympathetic activity (recorded from the inferior cardiac or renal nerve) accompanied by a rise of the arterial blood pressure and of the heart rate. Intravenous injection of lithium chloride or hydroxybutyrate resulted in lowering of the sympathetic activity, arterial blood pressure, and heart rate, and led to the recovery of the sinus rhythm.


Rgs6 is required for adult maintenance of dopaminergic neurons in the ventral substantia nigra.
Parkinson disease (PD) is characterized by the preferential, but poorly understood, vulnerability to degeneration of midbrain dopaminergic (mDA) neurons in the ventral substantia nigra compacta (vSNc). These sensitive mDA neurons express Pitx3, a transcription factor that is critical for their survival during development. We used this dependence to identify, by flow cytometry and expression profiling, the negative regulator of G-protein signaling Rgs6 for its restricted expression in these neurons. In contrast to Pitx3-/- mDA neurons that die during fetal (vSNc) or post-natal (VTA) period, the vSNc mDA neurons of Rgs6-/- mutant mice begin to exhibit unilateral signs of degeneration at around 6 months of age, and by one year cell loss is observed in a fraction of mice. Unilateral cell loss is accompanied by contralateral degenerating neurons that exhibit smaller cell size, altered morphology and reduced dendritic network. The degenerating neurons have low levels of tyrosine hydroxylase (TH) and decreased nuclear Pitx3; accordingly, expression of many Pitx3 target gene products is altered, including Vmat2, Bdnf, Aldh1a1 (Adh2) and Fgf10. These low TH neurons also express markers of increased dopamine signaling, namely increased DAT and phospho-Erk1/2 expression. The late onset degeneration may reflect the protective action of Rgs6 against excessive DA signaling throughout life. Rgs6-dependent protection is thus critical for adult survival and maintenance of the vSNc mDA neurons that are most affected in PD.


[Dystonic movement of the left upper limb in a case of the right pontine hemorrhage].
We report a 69-year-old woman who presented with dystonic movement in the left upper limb. She also had left hemiparesis and sensory disturbance in the right face and the left half of the body, pseudoathetosis in the left hand, and hotness, swelling, and lead-pipe rigidity in the left upper limb. The dystonic movement was presented mainly in the proximal part of the left upper limb, and was induced by voluntary movements; for example, when she was ordered to shake hands, the left shoulder always abducted with the flexion of the left elbow. Brain MRI showed a fresh hemorrhage in the dorsal part of the right middle pons including the base and the tegmentum, old infarctions in the right postero-lateral thalamus, putamen, and right parietal lobe. The dystonic movement persisted for 2 weeks, and hotness and swelling in the left upper limb lasted for 2 months, while the rigidity and pseudoathetosis persisted for 7 months or more despite medication.


Estimation of effective connectivity via data-driven neural modeling.
This research introduces a new method for functional brain imaging via a process of model inversion. By estimating parameters of a computational model, we are able to track effective connectivity and mean membrane potential dynamics that cannot be directly measured using electrophysiological measurements alone. The ability to track the hidden aspects of neurophysiology will have a profound impact on the way we understand and treat epilepsy. For example, under the assumption the model captures the key features of the cortical circuits of interest, the framework will provide insights into seizure initiation and termination on a patient-specific basis. It will enable investigation into the effect a particular drug has on specific neural populations and connectivity structures using minimally invasive measurements. The method is based on approximating brain networks using an interconnected neural population model. The neural population model is based on a neural mass model that describes the functional activity of the brain, capturing the mesoscopic biophysics and anatomical structure. The model is made subject-specific by estimating the strength of intra-cortical connections within a region and inter-cortical connections between regions using a novel Kalman filtering method. We demonstrate through simulation how the framework can be used to track the mechanisms involved in seizure initiation and termination.


Photodynamic action of merocyanine 540 on artificial and natural cell membranes: involvement of singlet molecular oxygen.
The photochemistry of merocyanine 540 (MC 540), a sensitizing dye that binds preferentially to leukemia and electrically excitable cells, has been investigated. MC 540-mediated photooxidation of histidine, arachidonate, and unsaturated phospholipid vesicles was assessed by spin label oximetry and shown to involve type II (singlet oxygen) chemistry. The dye was also shown to be a potent sensitizer of lipid peroxidation in a natural cell membrane, the erythrocyte ghost. Inhibition by azide, stimulation by 2H2O, and identification of the cholesterol product 5 alpha-cholest-6-ene-3 beta,5-diol in this system, all were consistent with singlet oxygen intermediacy. Finally, MC 540 was found to be considerably more phototoxic to K-562 leukemia cells in 2H2O than in H2O. We conclude that singlet oxygen plays a major role in the phototherapeutic effects of this dye.


Expectation modulates neural responses to pleasant and aversive stimuli in primate amygdala.
Animals and humans learn to approach and acquire pleasant stimuli and to avoid or defend against aversive ones. However, both pleasant and aversive stimuli can elicit arousal and attention, and their salience or intensity increases when they occur by surprise. Thus, adaptive behavior may require that neural circuits compute both stimulus valence--or value--and intensity. To explore how these computations may be implemented, we examined neural responses in the primate amygdala to unexpected reinforcement during learning. Many amygdala neurons responded differently to reinforcement depending upon whether or not it was expected. In some neurons, this modulation occurred only for rewards or aversive stimuli, but not both. In other neurons, expectation similarly modulated responses to both rewards and punishments. These different neuronal populations may subserve two sorts of processes mediated by the amygdala: those activated by surprising reinforcements of both valences-such as enhanced arousal and attention-and those that are valence-specific, such as fear or reward-seeking behavior.


Structural requirements for phosphorylation of myosin regulatory light chain from smooth muscle.
Site-directed and chimeric mutations of myosin regulatory light chains were used to identify residues important for phosphorylation of Ser19 by smooth muscle myosin light chain kinase. Arg16 and hydrophobic residues C-terminal of Ser19 in smooth muscle light chain were important substrate determinants in the intact protein. However, changes in the kinetic properties with mutations in the light chain were substantially smaller than results reported with structurally similar synthetic peptide substrates. These results together with the low Vmax value for short peptide substrates containing the consensus phosphorylation sequence suggest that there may be additional sites of interactions between the kinase and protein substrate. Chimeras of skeletal and smooth muscle light chains were constructed with exchanges at the N terminus and subdomains I, II, III, and IV. Analysis of results obtained on the kinetic properties for phosphorylation showed that subdomains I and II contribute to high Vmax values. Thus, a region distant from the consensus phosphorylation sequence in smooth muscle light chain is also an important substrate determinant for myosin light chain kinase.


Kinetic and equilibrium isotherm studies for the adsorptive removal of Brilliant Green dye from aqueous solution by rice husk ash.
The present study deals with the adsorption of Brilliant Green (BG) on rice husk ash (RHA). RHA is a solid waste obtained from the particulate collection equipment attached to the flue gas lines of rice husk fired boilers. Batch studies were performed to evaluate the influences of various experimental parameters like initial pH (pH0), contact time, adsorbent dose and initial concentration (C0) on the removal of BG. Optimum conditions for BG removal were found to be pH0 approximately 3.0, adsorbent dose approximately 6 g L(-1) of solution and equilibrium time approximately 5 h for the C0 range of 50-300 mg L(-1). Adsorption of BG followed pseudo-second-order kinetics. Intra-particle diffusion does not seem to control the BG removal process. Equilibrium isotherms for the adsorption of BG on RHA were analyzed by Freundlich, Langmuir, Redlich-Peterson (R-P), Dubnin-Radushkevich (D-R), and Temkin isotherm models using a non-linear regression technique. Langmuir and R-P isotherms were found to best represent the data for BG adsorption onto RHA. Adsorption of BG on RHA is favourably influenced by an increase in the temperature of the operation. Values of the change in entropy (DeltaS0) and heat of adsorption (DeltaH0) for BG adsorption on RHA were positive. The high negative value of change in Gibbs free energy (DeltaG0) indicates the feasible and spontaneous adsorption of BG on RHA.


UHPLC/MS2-based approach for the comprehensive metabolite profiling of bean (Vicia faba L.) by-products: A promising source of bioactive constituents.
Today, by-products generated from the agro-industrial practices are considered a key source of bioactive and functional components, that can be used for their nutritional and added value properties. New aspects concerning the use of these wastes as by-products in food production additives or supplements with high nutritional and medicinal value have gained substantial interest, due to their possession of economically high-value products. In this sense, the present study describes a thorough characterization of phytochemical compounds from hydro-methanolic extract of broad beans testa by using ultra-high performance liquid chromatography (UHPLC) hyphenated with quadrupole-time-of-flight tandem mass spectrometry (QTOF-MS). The proposed analytical technique provides tentative characterization of 134 phenolic and other phytochemical compounds in the Vicia faba extract, most of which have not been described so far in broad beans. Thus, >85 phytochemicals (Amino acids, phenolic acids, flavonoids, lignans, and terpenoids derivatives) are being reported herein in broad beans pods for the first time. The characterization process was carried out using MS and MS2 data provided by the ESI-qTOF-MS, along with the use of the relevant literature based on the same botanical family. The data obtained demonstrates that the agro-industrial by-product could potentially be utilized as a promising source of bioactive ingredients to design new functional foods and nutraceuticals with a valuable future market. Furthermore, the obtained data may form a basis for future quantitative and bioavailability studies, which will be the next step in this present work.


A vectorized sequence-coupling model for predicting HIV protease cleavage sites in proteins.
What kind of peptide sequences can be cleaved by HIV protease, and what kind cannot be? This is a crucially important problem in designing effective inhibitors against HIV protease as potential drugs for AIDS therapy. To tackle this problem, a sequence-coupling and vectorized model is proposed for predicting the cleavability of oligopeptides by proteases with multiple and extended specificity subsites. In comparison with existing methods, the new method has proved to be an improvement in both the accuracy of the model and the rationality of the statistical treatment. Meanwhile, the Monte Carlo sampling procedure introduced here has also proved to be very useful in dealing with the situation when the experimental data are insufficiently sampled for complete statistics. Owing to its very high rate of correct prediction, it is expected that the new method can be a useful technique for helping to find effective inhibitors of HIV protease, which is one of the targets in designing potential drugs against AIDS. The principle of the new method can also be applied to analyzing the specificity of any multi-subsite enzyme.